Superoxide dismutases in malignant cells and human tumors

Reactive oxygen metabolites have multifactorial effects on the regulation of cell growth and the capacity of malignant cells to invade. Overexpression of the superoxide dismutases (SODs) in vitro increases cell differentiation, decreases cell growth and proliferation, and can reverse a malignant phenotype to a nonmalignant one. The situation in vivo is more complex due to multiple interactions of tumor cells with their environment. Numerous in vivo studies show that the superoxide dismutases can be highly expressed in aggressive human solid tumors. Furthermore, high SOD has occasionally been associated with a poor prognosis and with resistance to cytotoxic drugs and radiation. Most of the apparent conflicts between the above in vitro and in vivo observations can be reconciled by considering the net redox status of tumor cells in different environments. Administering high concentrations of SOD to cells in vitro is usually associated with a non- or less malignant phenotype, whereas secondary induction of SOD in tumors in vivo can be associated with an aggressive malignant transformation probably due to the altered (oxidative) redox state in the malignant cells. This concept suggests that for many types of tumors antioxidants could be used to diminish the invasive capability of malignant cells.